The genomic landscape of juvenile myelomonocytic leukemia.

Journal: Nature Genetics
Published:
Abstract

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription. Notably, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.

Authors
Elliot Stieglitz, Amaro Taylor Weiner, Tiffany Chang, Laura Gelston, Yong-dong Wang, Tali Mazor, Emilio Esquivel, Ariel Yu, Sara Seepo, Scott Olsen, Mara Rosenberg, Sophie Archambeault, Ghada Abusin, Kyle Beckman, Patrick Brown, Michael Briones, Benjamin Carcamo, Todd Cooper, Gary Dahl, Peter Emanuel, Mark Fluchel, Rakesh Goyal, Robert Hayashi, Johann Hitzler, Christopher Hugge, Y Liu, Yoav Messinger, Donald Mahoney, Philip Monteleone, Eneida Nemecek, Philip Roehrs, Reuven Schore, Kimo Stine, Clifford Takemoto, Jeffrey Toretsky, Joseph Costello, Adam Olshen, Chip Stewart, Yongjin Li, Jing Ma, Robert Gerbing, Todd Alonzo, Gad Getz, Tanja Gruber, Todd Golub, Kimberly Stegmaier, Mignon Loh